Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction

Greenhill, Claire J., Jones, Gareth W., Nowell, Mari A., Newton, Zarabeth, Harvey, Ann K., Moideen, Abdul N., Collins, Fraser L., Bloom, Anja C., Coll, Rebecca C., Robertson, Avril A. B., Cooper, Matthew A., Rosas, Marcela, Taylor, Philip R., O'Neill, Luke A., Humphreys, Ian R., Williams, Anwen S. and Jones, Simon A. (2014) Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction. Arthritis Research and Therapy, 16 4: . doi:10.1186/s13075-014-0419-y

Author Greenhill, Claire J.
Jones, Gareth W.
Nowell, Mari A.
Newton, Zarabeth
Harvey, Ann K.
Moideen, Abdul N.
Collins, Fraser L.
Bloom, Anja C.
Coll, Rebecca C.
Robertson, Avril A. B.
Cooper, Matthew A.
Rosas, Marcela
Taylor, Philip R.
O'Neill, Luke A.
Humphreys, Ian R.
Williams, Anwen S.
Jones, Simon A.
Title Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction
Journal name Arthritis Research and Therapy   Check publisher's open access policy
ISSN 1478-6362
Publication date 2014-08-30
Year available 2014
Sub-type Article (original research)
DOI 10.1186/s13075-014-0419-y
Open Access Status DOI
Volume 16
Issue 4
Total pages 10
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
Activation of the inflammasome has been implicated in the pathology of various autoinflammatory and autoimmune diseases. While the NLRP3 inflammasome has been linked to arthritis progression, little is known about its synovial regulation or contribution to joint histopathology. Regulators of inflammation activation, such as interleukin (IL)-10, may have the potential to limit the inflammasome-driven arthritic disease course and associated structural damage. Hence, we used IL-10-deficient (IL-10KO) mice to assess NLRP3 inflammasome-driven arthritic pathology.

Antigen-induced arthritis (AIA) was established in IL-10KO mice and wild-type controls. Using histological and radiographic approaches together with quantitative real-time PCR of synovial mRNA studies, we explored the regulation of inflammasome components. These were combined with selective blocking agents and ex vivo investigative studies in osteoclast differentiation assays.

In AIA, IL-10KO mice display severe disease with increased histological and radiographic joint scores. Here, focal bone erosions were associated with increased tartrate-resistant acid phosphatase (TRAP)-positive cells and a localized expression of IL-1β. When compared to controls, IL-10KO synovium showed increased expression of Il1b, Il33 and NLRP3 inflammasome components. Synovial Nlrp3 and Casp1 expression further correlated with Acp5 (encoding TRAP), while neutralization of IL-10 receptor signaling in control mice caused increased expression of Nlrp3 and Casp1. In ex vivo osteoclast differentiation assays, addition of exogenous IL-10 or selective blockade of the NLRP3 inflammasome inhibited osteoclastogenesis.

These data provide a link between IL-10, synovial regulation of the NLRP3 inflammasome and the degree of bone erosions observed in inflammatory arthritis.
Keyword Rheumatology
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 19234
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
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